This study aims to design and synthesize a number of novel pyran, thiophene, and pyridine derivatives incorporating thiazole ring and evaluate their antitumor inhibition (μM) as significant anticancer agents. The reactivity of compound 1 [2‐(4‐oxo‐4,5‐dihydrothiazol‐2‐yl)acetonitrile] towards different chemical reagents was described. Furthermore, the reactivity of all the newly synthesized products was evaluated. The most active compounds towards all the three tumor cancer cell lines used such as MCF‐7 (breast adenocarcinoma), NCI‐H460 (non‐small cell lung cancer) and SF‐268 (CNS cancer), and normal fibroblasts human cell line (WI‐38) were compounds 6d, 8, and 10b, which compared with the antiproliferative effects of the reference control doxorubicin. Also, some of the novel compounds indicate higher inhibition than doxorubicin against some of the cancer cell lines used such as 6c (especially towards MCF‐7) and 2b, 6b (especially towards SF‐268).

ABSTRACT. A new approaches for the synthesis of novel pyrazolo[1,5-a]quinazoline 8a-f and pyrazolo[1,5-a]quinazolin-6-one 10a-s and 12a-s derivatives were obtained using 4-(2-phenylhydrazono)-4H-pyrazol-3-amine derivatives 5a-f via their multi-component reactions. The later pyrazole derivatives were prepared via arylhydrazone derivatives 3a-f. The structures of the synthesized compounds were established based on their respective analytical data. On the other hand, the cytotoxic effects of the synthesized compounds were obtained against the six cancer cell lines, namely A549, HT-29, MKN-45, U87MG, SMMC-7721 and, H460 utilizing foretinib as the positive control and the standard MTT assay in vitro. The obtained results showed that compounds 8c, 8f, 10c, 10i, 10l, 10p, 10s, 12c, 12i, 12l, 12p and, 12s were the most cytotoxic compounds. In most cases the presence of the electronegative Cl group enhanced the cytotoxicity of the tested compound.   KEY WORDS: Multi-component reactions, Pyrazolo[1,5-a]quinazoline, Pyrazolo[1,5-a]quinazolin-6-one, Cytotoxicity Bull. Chem. Soc. Ethiop. 2023, 37(3), 717-734.                                                                DOI: https://dx.doi.org/10.4314/bcse.v37i3.14